Human bronchus, pancreatic duct and esophagus can be cultured for several weeks in a chemically-defined medium. This controlled experimental setting provides an excellent in vitro system to study the metabolism of chemical carcinogens including those found in tobacco smoke and the environment. Several classes of chemical carcinogens, polynuclear aromatic hydrocarbons, N-nitrosamines, hydrazines, and mycotoxins can be metabolically activated by human tissues. The metabolic pathways leading to the formation of DNA adducts in cultured bronchus have been defined for benzo(a)pyrene, aflatoxin B1, 1,2,-dimethyl hydrazine and dimethylnitrosamine. The adducts between these carcinogens and DNA in human bronchus are essentially the same as those found in experimental animals in which these chemicals are carcinogenic. When different people are compared a marked variation in binding levels are found, e.g., the inter individual variation in the binding of BP to DNA in cultured human bronchus was 75-fold (100 patients). Nontumorous bronchi from patients with epidermoid carcinomas of the lung bind significantly more BP to DNA when compared to specimens from patients with either no cancer or adenocarcinomas of the lung.